Koura Minoru, Matsuda Takayuki, Okuda Ayumu, Watanabe Yuichiro, Yamaguchi Yuki, Kurobuchi Sayaka, Matsumoto Yuuki, Shibuya Kimiyuki
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd, 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan.
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd, 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan.
Bioorg Med Chem Lett. 2015 Jul 1;25(13):2668-74. doi: 10.1016/j.bmcl.2015.04.080. Epub 2015 May 5.
A novel series of 1,3-bistrifluoromethylcarbinol derivatives that act as liver X receptor (LXR) β-selective agonists was discovered. Structure-activity relationship studies led to the identification of molecule 62, which was more effective (Emax) and selective toward LXRβ than T0901317 and GW3965. Furthermore, 62 decreased LDL-C without elevating the plasma TG level and significantly suppressed the lipid-accumulation area in the aortic arch in a Bio F1B hamster fed a diet high in fat and cholesterol. We demonstrated that our LXRβ agonist would be potentially useful as a hypolipidemic and anti-atherosclerotic agent. In this manuscript, we report the design, synthesis and pharmacology of 1,3-bistrifluoromethylcarbinol derivatives.
